PROTECTION AGAINST ENDOTOXIC-SHOCK BY BACTERICIDAL PERMEABILITY-INCREASING PROTEIN IN RATS

Bactericidal/permeability-increasing protein (BPI) is a neutrophil pri mary granule protein that inhibits effects of LPS in vitro., The curre nt study examined the effects of BPI on hemodynamics, mortality, and c irculating endotoxin and cytokines in conscious rats with endotoxic sh ock, Catheters were implanted into the right femoral artery and vein, 1 d later, human recombinant BPI (10 mg/kg) or vehicle was intravenous ly injected immediately, 30 min, or 2 h after intravenous injection of LPS (7.5 mg/kg). Mean arterial pressure (MAP) and heart rate were mon itored and blood was collected before and after injection, BPI given i mmediately or 30 min after LPS prevented the LPS-induced reduction in MAP at 4-8 h-and markedly reduced mortality, BPI given 2 h after LPS i njection had no protective effect. BPI treated immediately after LPS r educed the circulating levels of endotoxin and IL-6 but increased the circulating levels of TNF, We propose that BPI exerts its protective e ffect through a TNF-independent mechanism, by inhibiting endotoxin-sti mulated production of IL-6.